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ISSN: 2161-0495 Journal of Clinical Toxicology Case Report

A Case of a Suicide Attempt by Taxus baccata Leaves Poisoning

Beñat de Alba Iriarte1*, Eva Lorea Gil Rodríguez1, Edurne Bereciartua Urbieta1, María Elena Redín Sarasola1, Txoan Ormazabal Zabala2, Mikel Díez Bengoechea2, María Asunción Vives Almandoz1, Adolfo Garrido Chércoles1, Oscar Quintela Jorge3 1Osakidetza Basque Health Service, Donostia University Hospital, Clinical Biochemistry Laboratory, Donostia-San Sebastián, Spain; 2Osakidetza Basque Health Service, Donostia University Hospital, Intensive Care Unit, Donostia-San Sebastián, Spain; 3National Institute of Toxicology and Forensic Sciences, Department of Madrid, Chemistry Service, Las Rozas de Madrid, Spain

ABSTRACT Taxus baccata is one of the most poisonous trees in the world. It contains taxanes and toxic alkaloids: the most dangerous one is the taxine. It is a fairly common plant in our environment and could be extremely dangerous; however, yew poisoning is quite rare. Cases may occur by voluntary or accidental ingestion. Therefore, the rapid orientation and diagnosis of suspected episode are important, in order to treat it quickly. There are no specific clinical or analytical alterations in this intoxication and it is very difficult to determine in each case the evolution of the episode. Patients who ingest a lethal dose frequently die due to cardiac arrest, in spite of resuscitation efforts. At present, no specific therapy exists. Therapeutic procedures reported in the literature are only referred to in published case reports, so there is insufficient evidence to recommend any treatment in yew poisoning. In our case report, we describe poisoning by ingestion of Taxus baccata leaves in a suicide attempt, its clinical evolution and its management and we do a brief review of the literature about yew poisoning. Keywords: 3,5-dimethoxyphenol; Cardiotoxicity; Poisoning; Taxine; Taxus baccata; Yew

ABBREVIATIONS: CASE PRESENTATION ECG: Electrocardiogram; GC: Gas Chromatography; MS: Mass 48-year-old man was transferred by ambulance to the emergency Spectrometry department of the hospital, with no symptoms, 2 hours after autolytic attempt by abundant yew leaves ingestion. He was INTRODUCTION aware of the arrival of the ambulance and he said that he was Taxus baccata (Common yew, English yew, or European yew), cutting yew leaves and ingesting them, although he could not native to western, central and southern Europe, is one of the specify the exact amount. The physical examination was normal and the analysis only presented respiratory alkalosis, mild most poisonous trees in the world. It contains taxanes (from 3 which antineoplastic drugs, such as paclitaxel, are obtained) and leukocytosis (13.75 × 10 /µL (3.8-10)) and increased lactate (4.66 toxic alkaloids. The most dangerous one is the taxine, a dose- mmol/L (<2)). dependent sodium and calcium channel antagonist. While in emergency room stay he suffered from abrupt reduced It is a fairly common plant in our environment and could be consciousness and ventricular fibrillation that had required extremely dangerous; however, yew poisoning is quite rare. The electrical cardioversion, 200 joules twice. Subsequently, he whole tree is toxic, except for the aril of its berries. Cases may presented aberrated rhythm with wide QRS and ventricular occur by voluntary or accidental ingestion. Therefore, the rapid tachycardia. Amiodarone (IV 300 mg) was administered and orientation and diagnosis of suspected episode are important, in orotracheal intubation and mechanic ventilation were order to treat it quickly. performed. Therefore, he entered the intensive care unit. The

Correspondence to: Beñat de Alba Iriarte, Osakidetza Basque Health Service, Donostia University Hospital, Clinical Biochemistry Laboratory, Donostia-San Sebastián, Spain, E-mail: [email protected] Received: May 26, 2020; Accepted: June 09, 2020; Published: June 16, 2020 Citation: Iriarte BA, Gil EL, Bereciartua E, Redín ME, Ormazabal T, Díez M, et al. (2020) A Case of a Suicide Attempt by Taxus baccata Leaves Poisoning. J ClinToxicol. 10:443. DOI: 10.35248/2161-0495.20.10.443 Copyright: © 2020 Iriarte BA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

J Clin Toxicol, Vol.10 Iss.4 No:1000443 1 Iriarte BA, et al. results of a second analysis were leukocytosis (20.96 × 103/µL troponin T (19.3 ng/L (0-14)) and creatine kinase (237 U/L (3.8-10)) and increased lactate 2.89 mmol/L (<2), high-sensitivity (0-189)). Rest of the analysis were normal (Table 1).

Table 1: Analysis results.

Reference Results values Parameters (Units) 18 March 18 March 18 March 19 March 20 March 21 March 17:45 19:35 21:25 8:15 8:15 8:25

Sodium (mEq/L) 137 136 138 140 135 142 [135-145]

Chlorine (mEq/L) 96 98 97 103 104 107 [93-110]

Potasium (mEq/L) 3.77 3.68 3.72 4.62 3.99 3.83 [3.3-5.1]

Glucose (mg/dL) 109 186 263 124 117 94 [70-110]

Bilirubin (mg/dL) - 1.19 - 1.67 1.71 1.29 [0-1.1]

Creatinine (mg/dL) 0.98 0.95 1.02 1.01 0.7 0.67 [0.70-1.20]

Total proteins (g/dL) 7.32 5.9 5.93 5.91 - - [6.6-8.7]

Calcium (mg/dL) 10.1 8.1 8.7 8.5 - - [8.6-10.2]

Lactate (mg/dL) 4.66 2.89 2.78 1.55 1.67 - [<2]

High-sensitivity troponin T (ng/L) - 19.3 110 99.9 - - [0-14]

NT-proBNP (pg/mL) - 96 217 1222 - - [0-300]

Creatine kinase (U/L) - 237 427 - - - [0-189]

C-reactive protein (mg/L) - 1.9 - 24.6 96.7 56.4 [0-5]

Procalcitonin (ng/mL) - - - 0.83 0.56 0.36 [<0.5]

Red blood cells (*106/µL) 5.17 4.83 5.15 5.08 4.11 4.14 [4.3-5.6]

Hemoglobin (g/dL) 15.5 14.7 15.8 15.4 12.7 12.5 [13-17]

White blood cells (*103/µL) 13.75 20.96 26.06 19.33 13.84 10.54 [3.8-10]

Platelets (*103/µL) 235 204 229 216 160 133 [140-400]

Prothrombin time (%) - 86 - 83 75 90 [70-140]

APTT (sec) - 26.4 - 29.6 33.8 31.4 [24-36]

pH 7.63 7.36 7.36 7.47 7.43 - [7.35-7.45]

pO2 (mmHg) 112 193 380 188 102 - [83-108]

pCO2 (mmHg) 15 32 37 32 36 - [35-48]

Bicarbonate (mmol/L) 15.8 18.1 20.9 23.3 23.9 - [21-28]

O2 saturation (%) 98.8 99.7 100.2 99.8 98.8 - [95-99]

Since admission, he had tendency to bradycardia (less than 50 beats/min). Nasogastric tube was placed and activated charcoal beats/min) alternating with wide QRS tachycardia (up to 110 and Mg sulfate (IV 1 g) were administered. Treatment with

J Clin Toxicol, Vol.10 Iss.4 No:1000443 2 Iriarte BA, et al.

vasopressor support with norepinephrine and inotropic support with dopamine was also initiated, and calcium gluconate (IV 200 mg) was given for the purpose of myocardial membrane stabilization. He had some episodes of pulseless ventricular tachycardia that required several attempts of electrical cardioversion, reversing the episodes to chaotic rhythms with wide QRS and tendency to bradycardia. Therefore, an external pacemaker was placed to recover the cardiac frequency and the blood pressure. Doctors called toxicology department that referred there is no antidote for this poisoning and recommended continuing with activated charcoal, forcing diuresis without alkalizing the urine and treating with vasoactive support. After 24 hours, he achieved progressive clinical and hemodynamic stabilization. The ECG, after this stabilization, showed signs compatible with Brugada Syndrome type I in V1-V2. Apparently, yew toxin interacts in the same sites (sodium channels) as in people who genetically have this syndrome. With Glasgow 15, the extubation proceeded without problems and the pacemaker was removed, after confirming by echocardiogram that he had no cardiac abnormalities. In analysis, leukocytes and cardiac enzymes were altered with good evolution. Given the normalization of the ECG and the absence of arrhythmic events in the next 72 hours, the episode was interpreted as secondary to the toxin of yew, so it was not considered convenient to adopt other measures. He fully recovered in a week. The final diagnosis was confirmed by the detection of 3,5- dimethoxyphenol, by GC/MS. Samples (EDTA blood and Figure 1: Taxus baccata in Usurbil, Gipuzkoa (Basque Country). heparin plasma) were analyzed by the Spanish National Institute of Toxicology and Forensic Sciences, 7 months after their obtention and preservation at 2-8°C. 3,5-dimethoxyphenol was The yew tree has been known since antiquity for its toxicity. It detected in both samples. was a sacred tree for the Celts. In ancient times, it was a desired species, particularly for its high quality wood, and was studied DISCUSSION both for its medicinal and poisonous properties. It was known Yew (Taxus spp.) is a coniferous tree of the Taxaceae family, as the “tree of death” by the Greeks and Romans and among the typical of mountainous areas with cool and humid ancient Galician, Asturian, Cantabrian and Vasconian environments. It contains taxanes and toxic alkaloids (such as populations of the Iberian Peninsula the practice of suicide with taxine). There are many species and one of them is Taxus baccata yew poison was widespread. It was part of some of their rituals, [1]. probably due to the extraordinary longevity of the plant, which makes it seem immortal. For this reason, in many parts of Taxus baccata is a species of the genus Taxus, one of the most Europe, individual ancient yew trees are considered monuments toxic trees in the world. It grows slowly, reaching a longevity up of nature and, therefore, they are protected and conserved. to 5000 years. They rarely form forests, being commonly found as isolated individuals. It is a conifer with a persistent leaf that Currently, yew (Taxus baccata) poisoning is very rare, being of can reach 20 meters high, although usually they don´t exceed extreme gravity or fatal if it happens. The tree contains a toxic the size of a small tree. The trunk is usually thick and short and substance called taxine that is dangerous and deadly. It is a can reach 4 meters in diameter. Its crown is pyramidal, very mixture of alkaloids that generate gastrointestinal irritation and dense and dark, with abundant branches and it projects a very cardiotoxic effects [2], since it antagonize the sodium and dense shade. The leaves, thin and dark green colour, are calcium channels in the myocyte causing heart paralysis at high grouped in spiral on the branch (Figure 1). doses. The lethal dose has been estimated at 50-100 grams of leaves, and the twigs and fallen leaves of the tree are as toxic as the fresh plant. Death can occur due to acute cardiotoxicity, although in most cases symptoms usually appear over the course of several hours and even days after exposure [3]. However, as toxins are absorbed quickly, in some cases death occurs by cardiotoxicity so early that no symptoms are manifested. Initial symptoms usually show up one hour after the ingestion and are mostly neurological (dizziness, muscle weakness, vertigo)

J Clin Toxicol, Vol.10 Iss.4 No:1000443 3 Iriarte BA, et al. and gastrointestinal (nausea, vomiting, diarrhea, abdominal oxygen) therapy, has been used in a number of cases of severe pain). Later, there might be mydriasis, seizures and lethargy, and yew poisoning to overcome the asystole phase and the authors finally, after 3 hours there is risk of having cardiovascular concluded that it was a positive intervention in the patient’s alterations (ventricular tachycardia, ventricular fibrillation, treatment. bradycardia and cardiac arrest). Apart from some cases of autolysis, there have been also cases of There are no specific analytical alterations in this intoxication. accidental poisoning in children that had been playing with the Taxine compound analysis is not made in clinical laboratories. plant [9], in animals that wandered around it [10] and in In order to confirm the final diagnosis, 3,5-dimethoxyphenol (a carpenters that had worked with its wood [11]. Usually, autolytic taxine metabolite) must be detected, by GC/MS in gastric attempts are life-threatening whilst non-voluntary poisonings content, blood, urine or tissues [4-6]. It is a product formed by have milder symptoms. the breakage of the glucosidic bond of the taxine and it has The prognosis of yew poisoning depends on the amount of toxic been proved as a useful biochemical marker in cases of ingested, a successful anamnesis and the rapid establishment of poisoning by any components of the tree. The diagnosis is not the treatment. possible if the intake of this plant is not suspected [7]. A thorough anamnesis and personal testimony from the patient or CONCLUSION the companions are necessary to direct the case as more common pathologies are usually suspected. A differential Although yew poisoning is quite rare, it is a common plant in diagnosis should be made with cardiac or neurological our environment, and it might be extremely dangerous due to conditions or poisoning by other toxins. its toxic alkaloids. There are no specific clinical or analytical alterations in this intoxication so the differential diagnosis Surprisingly, most nonintentional ingestions are asymptomatic should be made with cardiac or neurological conditions or and require minimal, if any, intervention. Intentional suicidal poisoning by other toxins. A thorough anamnesis and personal attempts can result in life-threatening cardiac toxicity, which can testimony from the patient or the companions are necessary to require aggressive supportive intervention. Most therapeutic direct the case. And it is very important to start the treatment as interventions that have been utilized in differents cases in the soon as possible. Final diagnosis is reached by the detection of literature have little proven benefit. In the case described, they the taxine metabolite 3,5-dimethoxyphenol. were guided by some indications of the literature in Spanish that mention that the treatment consists on basic symptomatic In the case described, the patient worsened abruptly, so it was measures, support (oxygen therapy and control of vital signs), a necessary to search information about yew poisoning in the quick gastric emptying, by vomit induction or gastric lavage, and literature to start treatment quickly. Because data on acute the administration of cathartics and activated charcoal. It is also severe yew poisoning is sparse, additional data and experience important to control cardiac arrhythmias, which may require will be necessary with differents treatment and interventions temporary pacemaker in severe cases [8]. However, because it is before any recommendations can be made as to their usefulness. generally unethical to perform controlled clinical trials in Fortunately, in our case, activated charcoal, vasoactive support, clinical toxicology and because of the rarity of yew poisoning, electrical cardioversion and an external pacemaker were enough the quality of the evidence for treatment interventions is weak. for stabilization and total recovery of the patient.

Various treatments have been proposed for yew poisoning. In ACKNOWLEDGMENTS general, gastric lavage, emesis, cathartics, are no more recommended in the management of acute poisoning and with Thanks to Spanish National Institute of Toxicology and Forensic yew massive ingestion, there is a high risk that the traditional Sciences (Instituto Nacional de Toxicología y Ciencias Forenses - management with antiarrhythmic drugs will be ineffective. In INTCF Madrid), to Clinical Biochemistry Laboratory and almost all the case reports, poisoning with yew tree constituents Intensive Care Unit of Donostia University Hospital and to resulted in effects that were highly resistant to pharmacological Faculty of Medicine and Nursing of the University of the Basque intervention. Of the various therapeutic interventions Country (UPV/EHU). attempted in some cases, such as atropine, lidocaine, amiodarone, sodium bicarbonate, digoxin immune fab, and REFERENCES hemodialysis, none have demonstrated a significant patient 1. Thomas PA, Polwart A. Taxus baccata L. J Ecol.2003;91:489-524. improvement. At present, there is insufficient evidence to 2. Piskac O, Stríbrny J, Rakovcova H, Maly M. Cardiotoxicity of yew. recommend any of these drugs routinely as a therapeutic Cor eta vasa.2015;57:234-8. intervention in yew poisoning. 3. Labossiere AW, Thompson DF. Clinical toxicology of yew The use of extracorporeal support should be reserved for poisoning. Ann Pharmacother.2018;52:591-9. patients not responsive to conventional treatments. 4. Grobosch T, Schwarze B, Stoecklein D, Binscheck T. Fatal poisoning with Taxus baccata. Quantification of paclitaxel (taxol Determination of efficacy or alteration of the natural history of A), 10-deacetyltaxol, baccatin III, 10-deacetylbaccatin III, a patient’s acute exposure with these invasive procedures is cephalomannine (taxol B), and 3,5-dimethoxyphenol in body lacking. Although it appears to be lifesaving in some cases of fluids by liquid chromatography-tandem mass spectrometry. J Anal severe acute poisoning, it is very difficult to determine how the Toxicol.2012;36:36-43. patient would have fared without it. Extracorporeal support, 5. Froldi R, Croci PF, Dell’Acqua L, Farè F, Tassoni G, et al. (2010) usually in the form of ECMO (extracorporeal membrane Preliminary gas chromatography with mass spectrometry

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